This award will continue to permit the candidate to concentrate on individual and collaborative research efforts on substance abuse. During the next five years the candidate will be significantly involved in studies of the neurobiological mechanisms of the self-administration of cocaine, heroin and cocaine/heroin combinations that include investigation of the role of cholinergic systems in cocaine self-administration (DA 03628) and investigation of the mechanisms underlying the ability of heroin to potentiate the reinforcing effects of cocaine demonstrated in this last funding period. This includes identification of the opioid receptor subtypes and their loci responsible for this potentiation (DA12498) and the use of a discrete trial procedure for drug presentation that may provide a rodent model for the transition from drug use to abuse (NIDA funded Center- DA06634 Project 3). During this last funding period international collaborations were initiated that included interactions with scientists in Russia and Mexico with common interests in the neurobiology of drug abuse which will continue and expand in scope. In addition, the candidate will continue to participate in the training of high school, undergraduate and graduate students in the responsible conduct of research. During this next funding period the major career development effort for the candidate will be to acquire expertise in functional genomics and proteomics which are expected to be integrated into his research program. Research, research development and research administration are expected to consume a significant portion of the candidate's efforts. This Senior Research Scientist award will continue to permit the candidate to broaden his and the institution's drug abuse research efforts to further enhance the impact of the drug abuse research program at Wake Forest University School of Medicine.